title: Bofutsushosan, a Japanese herbal (Kampo) medicine, attenuates progression of nonalcoholic steatohepatitis in mice.
abstract: BACKGROUND
  Obesity-induced liver disease (nonalcoholic fatty liver disease, NAFLD) is now the commonest cause of chronic liver disease in affluent nations. There are presently no proven treatments for NAFLD or its more severe stage, nonalcoholic steatohepatitis (NASH). Bofutsushosan (BTS), a Japanese herbal (Kampo) medicine, long used as an anti-obesity medicine in Japan and other Asian countries, has been shown to reduce body weight and improve insulin resistance (IR) and hepatic steatosis. The precise mechanism of action of BTS, however, remains unclear. To evaluate the ability of BTS to prevent the development of NASH, and determine the mediators and pathways involved.
  
  
  METHODS
  C57BL/6 mice were injected intra-peritoneally with gold-thioglucose and fed a high-fat diet (HF) or HF diet admixed with either 2 or 5 % BTS for 12 weeks. The effectiveness of BTS in attenuating features of NASH and the mechanisms through which BTS attenuated NASH were then assayed through an assessment of the anthropometric, radiological, biochemical and histological parameters.
  
  
  RESULTS
  BTS attenuated the progression of NASH through induction of adiponectin and its receptors along with an induction of PPAR-α and PPAR-γ, decreased expression of SREBP-1c, increased hepatic fatty acid oxidation and increased hepatic export of triglycerides. BTS moreover, reduced IR through phosphorylation of the protein kinase, Akt.
  
  
  CONCLUSIONS
  BTS through induction of adiponectin signaling and Akt attenuated development of NASH. Identification of the active entity in BTS should allow development of novel treatments for NASH.
authors.affiliation: Department of Gastroenterology and Hepatology, Kochi Medical School, Kohasu, Nankoku, Kochi, 783-8505, Japan, onom@kochi-u.ac.jp.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ono
authors.forename: Mitsunari
authors.initials: M
authors.lastname: Ogasawara
authors.forename: Akira
authors.initials: A
authors.lastname: Hirose
authors.forename: Sachiko
authors.initials: S
authors.lastname: Mogami
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Ootake
authors.forename: Kosuke
authors.initials: K
authors.lastname: Aritake
authors.forename: Takuma
authors.initials: T
authors.lastname: Higuchi
authors.forename: Nobuto
authors.initials: N
authors.lastname: Okamoto
authors.forename: Shuji
authors.initials: S
authors.lastname: Sakamoto
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Urade
authors.forename: Toshiji
authors.initials: T
authors.lastname: Saibara
authors.forename: Jude A
authors.initials: JA
authors.lastname: Oben
mesh_terms: D052242:Adiponectin / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D006051:Aurothioglucose / Q000494:pharmacology; D015153:Blotting, Western; D059305:Diet, High-Fat; D018450:Disease Progression; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005951:Glucose Tolerance Test; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D020835:Medicine, Kampo / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy*; D009765:Obesity / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D014057:Tomography, X-Ray Computed
chemical_list: D052242:Adiponectin; D004365:Drugs, Chinese Herbal; C098310:bofu-tsusho-san; D006051:Aurothioglucose